a Department of Critical Care Medicine , Nanfang Hospital, Southern Medical University , Guangzhou , China.
b Department of Pathophysiology , Guangdong Provincial Key Laboratory of Shock and Microcirculation Research, Southern Medical University , Guangzhou , China.
Free Radic Res. 2019 Feb;53(2):139-149. doi: 10.1080/10715762.2018.1549732. Epub 2018 Dec 26.
As a nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase, SIRT3 is highly expressed in tissues with high metabolic turnover and mitochondrial content. It has been demonstrated that SIRT3 plays a critical role in maintaining normal mitochondrial biological function through reversible protein lysine deacetylation. SIRT3 has a variety of substrates that are involved in mitochondrial biological processes such as energy metabolism, reactive oxygen species production and clearance, electron transport chain flux, mitochondrial membrane potential maintenance, and mitochondrial dynamics. In the suppression of SIRT3, functional deficiencies of mitochondria contribute to the development of various cardiovascular disorders. Activation of SIRT3 may represent a promising therapeutic strategy for the improvement of mitochondrial function and the treatment of relevant cardiovascular disorders. In the current review, we discuss the emerging roles of SIRT3 in mitochondrial derangements and subsequent cardiovascular malfunctions, including cardiac hypertrophy and heart failure, ischemia-reperfusion injury, and endothelial dysfunction in hypertension and atherosclerosis.
作为烟酰胺腺嘌呤二核苷酸（NAD）依赖性蛋白去乙酰化酶，SIRT3 在代谢周转率和线粒体含量高的组织中高度表达。已经证明，SIRT3 通过可逆的蛋白赖氨酸去乙酰化作用在维持正常线粒体生物学功能方面发挥着关键作用。SIRT3 有多种底物，参与线粒体生物学过程，如能量代谢、活性氧产生和清除、电子传递链通量、线粒体膜电位维持和线粒体动力学。在 SIRT3 的抑制中，线粒体的功能缺陷导致各种心血管疾病的发展。SIRT3 的激活可能代表改善线粒体功能和治疗相关心血管疾病的有前途的治疗策略。在本综述中，我们讨论了 SIRT3 在线粒体紊乱和随后的心血管功能障碍中的新作用，包括心脏肥大和心力衰竭、缺血再灌注损伤以及高血压和动脉粥样硬化中的内皮功能障碍。
